Cytomegalovirus (CMV) is the most common recognized cause of viral-induced psychomotor retardation. As many as 5,000 infants are born in the U.S. each year with neurologic, psychomotor, percentual or behavioral abnormalities due to CMV. We have found, and others have confirmed that infants with active CMV infections have a defect in CMV-specific cell-mediated immunity (CMI) that can be detected by a lymphocyte proliferation assay. We plan to further investigate this profound defect in lymphocyte proliferation to CMV antigen by performing kinetic and cell purification and mixing experiments designed to probe the mechanics of and the cell subpopulations responsible for intact recognition of CMV antigen. In an open study of 10 infants, we found that administration of transfer factor (TF) prepared from donors known to have positive lymphocyte proliferation responses to CMV was associated with acquisition of an in vitro lymphocyte proliferative response in the infants and diminuation or cessation of viruria. We now propose a randomized, placebo-controlled, double-blind study of TF in congenital or perinatal CMV infections. TF will be prepared as a single lot from a pool of immune donors. Viruria and antibody responses in recipients of TF or placebo will be quantitated, CMI studied by lymphocyte proliferation and interferon production, and responding T-cell subsets characterization by the use of murine monoclonal antibodies. The role of monocytes and macrophages in recognition of CMV antigen will be examined. This project should provide important information on the cell phenotypes responsible for intact CMI to CMV. If observed results of the double-blind TF trial follow present patterns, an effect of TF on in vitro lymphocyte proliferation to CMV antigen could be demonstrated within 3 years.